title: Potentiation of chloroquine activity against Plasmodium falciparum by the peroxidase-hydrogen peroxide system.
abstract: In this study, we examined the potential interactions between antimalarial (chloroquine, quinine, and mefloquine) and oxidant reagents. The data indicate that their effects enhance those of one another in vitro. The viability of Plasmodium falciparum in culture was assessed by [3H]hypoxanthine incorporation during 24 h of incubation in the presence of lactoperoxidase, glucose-glucose oxidase, hydrogen peroxide, chloroquine, quinine, and mefloquine, either alone or in combination. At subinhibitory concentrations, a significant inhibition was produced by the following combinations: lactoperoxidase plus hydrogen peroxide, lactoperoxidase plus glucose-glucose oxidase, lactoperoxidase plus hydrogen peroxide or glucose-glucose oxidase plus chloroquine or quinine but not with mefloquine. Deletion of any component from the system markedly decreased the toxic effect on P. falciparum. This toxic effect was not inhibited by catalase. These results indicate that the peroxidase-hydrogen peroxide system and antimalarial drugs can potentiate each other to inhibit the growth of P. falciparum.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 13 et Départment de Biologie Parasitaire, Hôpital Claude Bernard, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Malhotra
authors.forename: D
authors.initials: D
authors.lastname: Salmon
authors.forename: J
authors.initials: J
authors.lastname: Le Bras
authors.forename: J L
authors.initials: JL
authors.lastname: Vilde
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D015767:Mefloquine / Q000494:pharmacology; D010544:Peroxidases / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011803:Quinine / Q000494:pharmacology
chemical_list: D007042:Hypoxanthines; D019271:Hypoxanthine; D002738:Chloroquine; D011803:Quinine; D006861:Hydrogen Peroxide; D010544:Peroxidases; D015767:Mefloquine